A qualitative evaluation of the oncologists', neurologists', and pain specialists' views on the management and care of chemotherapy-induced peripheral neuropathy in The Netherlands.

PURPOSE: In treating cancer, different chemotherapy regimens cause chemotherapy-induced peripheral neuropathy (CIPN). Despite recent international guidelines, a gold standard for diagnosis, treatment, and care is lacking. To identify the current clinical practice and the physicians' point of view and ideas for improvement, we evaluated CIPN care by interviewing different specialists involved. METHODS: We performed semi-structured, audio-recorded, transcribed, and coded interviews with a purposive sample of oncologists, pain specialists, and neurologists involved in CIPN patients' care. Data is analyzed by a constant comparative method for content analysis, using ATLAS.ti software. Codes, categories, and themes are extracted, generating common denominators and conclusions. RESULTS: With oncologists, pain specialists, and neurologists, nine, nine, and eight interviews were taken respectively (including three, two, and two interviews after thematic saturation occurred). While useful preventive measures and predictors are lacking, patient education (e.g., on symptoms and timely reporting) is deemed pivotal, as is low-threshold screening (e.g., anamnesis and questionnaires). Diagnosis focusses on a temporal relationship to chemotherapy, with adjuvant testing (e.g., EMG) used in severe or atypical cases. Symptomatic antineuropathic and topical medication are often prescribed, but personalized and multidimensional care based on individual symptoms and preferences is highly valued. The limited efficacy of existing treatments, and the lack of standardized protocols, interdisciplinary coordination, and awareness among healthcare providers pose significant challenges. CONCLUSION: Besides the obvious need for better therapeutic options, and multidisciplinary exploration of patients' perspectives, a structured and collaborative approach towards diagnosis, treatment, referral, and follow-up, nurtured by improving knowledge and use of existing CIPN guidelines, could enhance care.

Successful ageing at work: The role of job characteristics in growth trajectories of work ability and motivation to work amongst older workers.

In order to age successfully at work, people need to maintain or improve their work ability and motivation to work. This implies a process that develops over time and can differ substantially between individuals. This study investigated whether different trajectories of perceived work ability and motivation to work can be distinguished between older employees over time and to what extent job demands and job resources are predictive of these different trajectories. We applied growth mixture modelling amongst 5799 employees of 45 years and older at four time points. We found five distinct groups of older workers that differed in their trajectories of perceived work ability and four types of groups of older workers that differed in their trajectories of their motivation to work. Higher levels of physical demands, mental demands, autonomy, supervisor support, and colleague support were less common in unfavourable trajectories. This study gives Human Resource Management practitioners insight into how jobs should be designed to stimulate successful ageing at work.

Patient-Reported Long-Term Outcomes After Free Vascularized Fibula Graft in Spinal Reconstruction: a 24-year Cohort.

PURPOSE: The use of free vascularized fibula grafts (FVFG) in complex spinal deformity surgery intends to allow for life-long stability of the spine with good long-term clinical outcome. However, these long-term outcomes of this technique are still lacking. The objective of this study is to report the long-term postoperative outcomes and establish the long-term viability of this method for spinal reconstruction. METHODS: A retrospective cohort study was conducted in all patients who underwent spinal reconstructive surgery utilizing a FVFG at a tertiary medical centre. Questionnaires taken from the participants were the Numeric Pain Rating Scale (NPRS), Oswestry Low Back Pain Disability (also known as Oswestry Disability Index (ODI)), Scoliosis Research Society 22r (SRS-22), the EQ-5D-5L and a self-assembled questionnaire regarding donor site comorbidities and patient satisfaction. RESULTS: Over a period of 24 years (1995-2019), we used FVFG for spinal reconstruction in 31 patients. A total of 25 patients were included in this study, 8 patients were deceased at the time of this study, and sixteen patients responded to the questionnaires. Patient satisfaction was rated 6.8 out of 10, the average SRS-22r score was 3.6, EQ-5D-5L score was 0.725, and the ODI score showed a minimal disability (0-20%) postoperatively. Overall complication-free survival was 8.9 years. Nine patients underwent a re-operation in the spinal area; five for the removal of the spinal instrumentation. CONCLUSION: Patients reported satisfied and good long-term outcomes following FVFG surgical procedure for complex spinal deformities. Therefore, considering the alternatives, this procedure provides a good long-term solution for complex spinal deformity surgery.

Self-Management Education for Bipolar Disorders: A Hermeneutic-Phenomenological Study on the Tacit Knowledge of Mental Health Nurses.

Background: Self-management of bipolar disorder (BD) education is a complex nursing intervention in which patients and informal caregivers are taught to be actively involved in self-monitoring and self-regulating activities. Some studies question if nurses are sufficiently equipped to deliver these educational tasks. Other studies suggest that nurses have gathered their knowledge implicitly by experience, but to date, this tacit knowledge is not described from the experiences of mental health nurses (MHNs) in ambulant BD care. Objective: To detect the tacit knowledge used by MHNs by interpreting their experiences in delivering self-management education to people with BD and their informal caregivers. Methods: A phenomenological-hermeneutical study amongst MHNs (N = 9) from three ambulant BD care clinics in the Netherlands. Face-to-face, open, in-depth interviews guided by a topic list, were conducted and transcribed verbatim prior to the hermeneutical analysis. Findings: We found five categories resembling the complex character of self-management interventions provided by MHNs: Building a trustful collaboration, Starting a dialogue about needs and responsibilities, Explaining BD, Utilizing mood monitoring instruments, and Conceptualizing self-management of BD. Conclusion: Eventually MHNs use tacit knowledge to cope with situations that demand an outside-the-box approach. Self-management education is partially trained and partially mastered through experience. Practice implications: In order to facilitate long-term self-management of BD, the collaboration of a supporting network is essential.

The in vitro mechanisms and in vivo efficacy of intravenous lidocaine on the neuroinflammatory response in acute and chronic pain.

INTRODUCTION: The neuroinflammatory response plays a key role in several pain syndromes. Intravenous (iv) lidocaine is beneficial in acute and chronic pain. This review delineates the current literature concerning in vitro mechanisms and in vivo efficacy of iv lidocaine on the neuroinflammatory response in acute and chronic pain. DATABASES AND DATA TREATMENT: We searched PUBMED and the Cochrane Library for in vitro and in vivo studies from July 1975 to August 2014. In vitro articles providing an explanation for the mechanisms of action of lidocaine on the neuroinflammatory response in pain were included. Animal or clinical studies were included concerning iv lidocaine for acute or chronic pain or during inflammation. RESULTS: Eighty-eight articles regarding iv lidocaine were included: 36 in vitro studies evaluating the effect on ion channels and receptors; 31 animal studies concerning acute and chronic pain and inflammatory models; 21 clinical studies concerning acute and chronic pain. Low-dose lidocaine inhibits in vitro voltage-gated sodium channels, the glycinergic system, some potassium channels and Gαq-coupled protein receptors. Higher lidocaine concentrations block potassium and calcium channels, and NMDA receptors. Animal studies demonstrate lidocaine to have analgesic effects in acute and neuropathic pain syndromes and anti-inflammatory effects early in the inflammatory response. Clinical studies demonstrate lidocaine to have advantage in abdominal surgery and in some neuropathic pain syndromes. CONCLUSIONS: Intravenous lidocaine has analgesic, anti-inflammatory and antihyperalgesic properties mediated by an inhibitory effect on ion channels and receptors. It attenuates the neuroinflammatory response in perioperative pain and chronic neuropathic pain.

Identifying and describing patients' learning experiences towards self-management of bipolar disorders: a phenomenological study.

ACCESSIBLE SUMMARY: Existing evidence suggest that patient education in promoting self-management strategies of bipolar disorder (BD) is effective. However, results across the full range of service users with BD vary. Learning experiences of service users look to be a crucial factor to take into account when designing, delivering, and evaluating effective interventions that promote self-management in chronic illness. What learning activities service users actually undertake themselves when self-managing BD that might explain varying success rates, and guide future self-management educational programmes has not been examined. Unlike previous studies that suggest that outcomes in self-management depend on individual learning activities, the current study found that learning to self-manage BD takes place in a social network that functions as a learning environment in which it is saved for service users to make mistakes and to learn from these mistakes. Especially, coping with the dormant fear of a recurrent episode and acknowledging the limitations of an individual approach are important factors that facilitate this learning process. Practitioners who provide patient education in order to promote self-management of BD should tailor future interventions that facilitate learning by reflecting on the own experiences of service users. Community psychiatric nurses should keep an open discussion with service users and caregivers, facilitate the use of a network, and re-label problems into learning situations where both play an active role in building mutual trust, thereby enhancing self-management of BD. ABSTRACT: Existing evidence suggest that self-management education of bipolar disorder (BD) is effective. However, why outcomes differ across the full range of service users has not been examined. This study describes learning experiences of service users in self-managing BD that provide a possible explanation for this varying effectiveness. We have conducted a phenomenological study via face-to-face, in-depth interviews, guided by a topic list, along service users with BD I or II (n = 16) in three specialised community care clinics across the Netherlands. Interviews were digitally recorded and transcribed verbatim prior to analysis in Atlas.ti 7. Unlike existing studies, which suggest that individual abilities of service users determine outcomes in self-management of BD, the current study found that self-management of BD is a learning process that takes place in a collaborative network. We identified five categories: acknowledgment of having BD, processing the information load, illness management, reflecting on living with BD, and self-management of BD. The success of self-management depends on the acknowledgment of individual limitations in learning to cope with BD and willingness to use a social network as a back-up instead. Especially, the dormant fear of a recurrent episode is a hampering factor in this learning process.

Impact of inspiratory muscle training in patients with COPD: what is the evidence?

A meta-analysis including 32 randomised controlled trials on the effects of inspiratory muscle training (IMT) in chronic obstructive pulmonary disease (COPD) patients was performed. Overall and subgroup analyses with respect to training modality (strength or endurance training, added to general exercise training) and patient characteristics were performed. Significant improvements were found in maximal inspiratory muscle strength (P(I,max); +13 cmH2O), endurance time (+261 s), 6- or 12-min walking distance (+32 and +85 m respectively) and quality of life (+3.8 units). Dyspnoea was significantly reduced (Borg score -0.9 point; Transitional Dyspnoea Index +2.8 units). Endurance exercise capacity tended to improve, while no effects on maximal exercise capacity were found. Respiratory muscle endurance training revealed no significant effect on P(I,max), functional exercise capacity and dyspnoea. IMT added to a general exercise programme improved P(I,max) significantly, while functional exercise capacity tended to increase in patients with inspiratory muscle weakness (P(I,max) <60 cmH2O). IMT improves inspiratory muscle strength and endurance, functional exercise capacity, dyspnoea and quality of life. Inspiratory muscle endurance training was shown to be less effective than respiratory muscle strength training. In patients with inspiratory muscle weakness, the addition of IMT to a general exercise training program improved P(I,max) and tended to improve exercise performance.

Epidemiology of work related neck and upper limb problems: psychosocial and personal risk factors (part I) and effective interventions from a bio behavioural perspective (part II).

Work related neck and upper limb symptoms have a multi-factorial origin. Possible risk factors are of a physical, psychosocial or personal origin. These factors can reinforce each other and their influence can also be mediated by cultural or societal factors. Initially, most research on neck and upper limb symptoms focused on work-related physical exposure. Nowadays, psychosocial work characteristics are recognized as important risk factors. Various models have been developed to offer frameworks for possible pathways, but their empirical support is still not conclusive. In part I of this paper an overview is presented of the results of recent epidemiological studies on work related psychosocial and personal risk factors for neck and upper limb symptoms. In addition, the interplay between these factors and the possible intermediate role of an individuals work style in this process is explored. In contrast to previous reviews, it is now possible to base the conclusions on the effect of work related psychosocial factors on neck and upper limb symptoms on quite a few longitudinal studies. These studies show that high work demands or little control at work are often related to these symptoms. However, this relationship is neither very strong nor very specific. Perceived stress is studied in not as many studies but more consistently related to neck and upper limb symptoms. This also applies to general distress or other pain (co-morbidity). Job dissatisfaction does not contribute to neck and upper limb symptoms. Too little research on personal characteristics is available to draw any conclusions. It is plausible that behavioural aspects, such as work style, are of importance in the etiology of work related upper limb symptoms. However, studies concerning these factors are promising but too scarce to draw conclusions. Future studies should address these behavioural aspects. In part II, the recent studies on the effectiveness of preventive measures for work related neck and upper limb problems are discussed. Few randomised or non randomised controlled trials have been carried out to evaluate the effectiveness of individual or organisational interventions to improve work related psychosocial factors. Very few have reported on the preventive effect for work related neck and upper limb symptoms. Therefore, there is a great need for additional high quality trials before any conclusions on effectiveness of bio-behavioural interventions for reduction of neck and upper limb problems and return to work after these symptoms can be made. From the low back pain intervention research can be learned that interventions should best be targeted to both the worker and the organisation and that interventions will only be successful when all stakeholders are involved.

Do work-related physical factors predict neck and upper limb symptoms in office workers?

OBJECTIVES: The objective of this study was to examine the influence of physical exposure at work on neck and upper limb symptoms in office workers. METHODS: Data were used from a prospective cohort study with a follow-up period of 3 years. Independent variables were physical exposure at work, observed and self-reported. Outcome measures were neck-shoulder symptoms and elbow-wrist-hand symptoms. Data were analyzed with the generalized estimating equation (GEE) method, with adjustment for age, gender, psychosocial work characteristics and the outcome at baseline. RESULTS: Neck rotation was associated with neck-shoulder symptoms in the analyses with observed data (OR: 1.57; CI: 0.99-2.50) as well as those with self-reported data (OR: 1.43; CI: 1.02-2.01). Neck extension was also statistically significantly associated with neck-shoulder symptoms (OR: 2.42; CI: 1.22-4.80), but only self-reported data were available. Neck flexion, self-reported wrist pronation, self-reported arm elevation and self-reported duration of computer work, were not associated with symptoms. An indication was found of an adverse effect on neck-shoulder symptoms of long working days and on elbow-wrist-hand symptoms of self-reported wrist flexion and full-time work or longer compared to part-time work. CONCLUSIONS: Only a limited number of work-related physical factors were related to neck and upper limb symptoms in office workers. Only neck rotation and self-reported neck extension were identified as risk factors for neck-shoulder symptoms.

Dose-response relation between physical activity and sick leave.

OBJECTIVE: To investigate the dose-response relation between moderate and vigorous physical activity and sick leave in a working population. METHODS: Data were used from three large Dutch databases: two continuous, cross sectional surveys among a representative sample of the Dutch population and one prospective cohort study. A distinction was made between duration, frequency and intensity of physical activity. The outcome measure was the number of days of sick leave. Analyses of variance were used to compare sick leave (in days) for workers with different amounts of physical activity, in particular workers meeting the physical activity recommendations v those who did not. Linear and logistic regression analyses were used to obtain effect estimates in the prospective cohort study, with the generalised estimating equation (GEE) method. RESULTS: No relation was found between moderate physical activity and sick leave. In two databases, workers meeting the recommendation of vigorous physical activity (active at a vigorous level for at least three times a week) had significantly less sick leave: more than one day over two months and more than four days over a year. The duration of vigorous physical activity was not associated with sick leave. CONCLUSION: Physical activity at a vigorous intensity level for at least three times a week, as in the CDC/ACSM recommendation, has a positive effect on sick leave.

Can strenuous leisure time physical activity prevent psychological complaints in a working population?

AIMS: To investigate the longitudinal relation between strenuous leisure time physical activity and psychological complaints (depression and emotional exhaustion) in a Dutch working population in order to find evidence for the preventive role of physical activity in the development of psychological complaints. METHODS: All data came from the Study on Musculoskeletal disorders, Absenteeism, Stress, and Health (SMASH), a three year follow up study that started between 1994 and 1995. The study population consisted of 1747 workers from 34 companies. Generalised estimating equation (GEE) analyses were performed to investigate the longitudinal relation between strenuous leisure time physical activity and psychological complaints using models with and without a time lag. Logistic regression analyses were performed to study the relation between physical activity and sickness absence due to psychological complaints during the three year follow up study. RESULTS: Only in workers with a sedentary job was strenuous leisure time physical activity (1-2 times per week) significantly associated with a reduced risk of future depression and emotional exhaustion. This was not the case for physical activity at higher frequencies (> or =3 times per week). There was a dose-response relation between strenuous leisure time physical activity and poor general health which was strongest in workers with a sedentary job. Strenuous leisure time physical activity (1-2 times per week) was associated with a lower risk of long term absenteeism (>21 days), whereas physical activity at a higher frequency was not. CONCLUSIONS: Results suggest that strenuous leisure time physical activity might play a role in the prevention of future psychological complaints, poor general health, and long term absenteeism in a working population. Workers with a sedentary job seem to benefit more from strenuous leisure time physical activity than workers without a sedentary job.

The effect of physical activity in leisure time on neck and upper limb symptoms.

BACKGROUND: : Little is known of the preventive effects of physical activity in leisure time on neck and upper limb symptoms. METHODS: : A cohort of 1742 employees was selected from a prospective cohort study with a follow-up period of 3 years. Independent variables were sporting activities and physically active commuting. Outcome measures were neck/shoulder symptoms and elbow/wrist/hand symptoms as well as sickness absence due to these symptoms. To analyze the data, the generalized estimating equation (GEE) method was used, with adjustment for individual characteristics, such as age, gender, lifestyle, and the outcome at baseline. RESULTS: : Practicing sports for at least 10 months a year decreased the risk of neck/shoulder symptoms (OR: 0.82; CI: 0.67-0.99), sickness absence (OR: 0.48; CI: 0.28-0.84), and long-term sickness absence (OR: 0.37; CI: 0.17-0.84) due to neck or upper limb symptoms. A high mean intensity (> or = 3 h per week) of sporting activities had less effect than the continuation of these activities throughout the year. CONCLUSION: : Sustained sporting activities have a favorable effect on neck/shoulder symptoms and on sickness absence due to neck or upper limb symptoms. An effect of physically active commuting could not be demonstrated, although there was a tendency towards a favorable effect on sickness absence.

Effect of sporting activity on absenteeism in a working population.

OBJECTIVES: To determine the effects of sporting activity on absenteeism in a working population. METHODS: Data were used from a prospective cohort study in a working population with a follow up period of 3 years and were collected with yearly questionnaires or collected from company records. Complete data on absenteeism, sporting activity, and potential confounders were collected for 1228 workers. ANOVA was used to test differences in frequency and duration of absenteeism, correlations were computed to measure the association between number of sporting years (divided by age) and frequency and duration of absenteeism, and survival analysis, according to the Cox proportional hazards model, was used to test differences in relative risk at absenteeism and recovery. All analyses were adjusted for age, gender, smoking, and alcohol consumption, and were stratified for employees with sedentary and with more active jobs. RESULTS: ANOVA showed a statistically significant higher mean duration of absenteeism among employees not practicing sports, of approximately 20 days over a period of 4 years. The survival analysis showed an increased relative risk at absenteeism (relative risk (RR) 1.09; confidence interval (CI) 1.01 to 1.18) and a decreased relative risk at recovery (RR 0.90; CI 0.85 to 0.95) for employees not practicing sports. The effect of sporting activity is larger in employees with sedentary work. No associations were found between number of sporting years and absenteeism. CONCLUSION: Employees practicing sports take sick leave significantly less often than their colleagues not practicing sports, while their periods of sick leave are shorter, especially when their work is sedentary.

Identification of critical domains and putative partners for the Caenorhabditis elegans spindle component LIN-5.

Successful cell division requires proper assembly, placement and functioning of the spindle apparatus that segregates the chromosomes. The Caenorhabditis elegans gene lin-5 encodes a novel coiled-coil component of the spindle required for spindle positioning and chromosome segregation. To gain further insights into lin-5 function, we screened for dominant suppressors of the partial loss-of-function phenotype associated with the mutation lin-5(ev571ts ), and isolated 68 suppressing mutations. Eight out of the ten suppressors sequenced contained intragenic missense mutations immediately upstream of the lesion in lin-5(ev571ts ). These probably help to stabilize protein-protein interactions mediated by the coiled-coil domain. This domain was found to be required for binding to several putative LIN-5 interacting (LFI) proteins identified in yeast two-hybrid screens. Interestingly, interaction with the coiled-coil protein LFI-1 was specifically reduced by the lin-5(ev571ts ) mutation and restored by a representative intragenic suppressor mutation. Immunostaining experiments showed that LIN-5 and LFI-1 may co-localize around the kinetochore microtubules during metaphase, indicating potential interaction in vivo. The coiled-coil domain of LIN-5 was also found to mediate homodimerization, while the C-terminal region of LIN-5 was sufficient for interaction with GPR-1, a recently identified component of a LIN-5 spindle-regulatory complex. A single amino-acid substitution in the N-terminal region of LIN-5, encoded by the e1457 allele, abolished all LIN-5 interactions. Taken together, our results indicate that the spindle functions of LIN-5 depend on interactions with multiple protein partners, and that these interactions are mediated through several different domains of LIN-5.

lin-35 Rb and cki-1 Cip/Kip cooperate in developmental regulation of G1 progression in C. elegans.

We have investigated the regulation of cell-cycle entry in C. elegans, taking advantage of its largely invariant and completely described pattern of somatic cell divisions. In a genetic screen, we identified mutations in cyd-1 cyclin D and cdk-4 Cdk4/6. Recent results indicated that during Drosophila development, cyclin D-dependent kinases regulate cell growth rather than cell division. However, our data indicate that C. elegans cyd-1 primarily controls G1 progression. To investigate whether cyd-1 and cdk-4 solely act to overcome G1 inhibition by retinoblastoma family members, we constructed double mutants that completely eliminate the function of the retinoblastoma family and cyclin D-Cdk4/6 kinases. Inactivation of lin-35 Rb, the single Rb-related gene in C. elegans, substantially reduced the DNA replication and cell-division defects in cyd-1 and cdk-4 mutant animals. These results demonstrate that lin-35 Rb is an important negative regulator of G1/S progression and probably a downstream target for cyd-1 and cdk-4. However, as the suppression by lin-35 Rb is not complete, cyd-1 and cdk-4 probably have additional targets. An additional level of control over G1 progression is provided by Cip/Kip kinase inhibitors. We demonstrate that lin-35 Rb and cki-1 Cip/Kip contribute non-overlapping levels of G1/S inhibition in C. elegans. Surprisingly, loss of cki-1, but not lin-35, results in precocious entry into S phase. We suggest that a rate limiting role for cki-1 Cip/Kip rather than lin-35 Rb explains the lack of cell-cycle phenotype of lin-35 mutant animals.

S and G2 phase roles for Cdk2 revealed by inducible expression of a dominant-negative mutant in human cells.

Cyclin-dependent kinase 2 (Cdk2) is essential for initiation of DNA synthesis in higher eukaryotes. Biochemical studies in Xenopus egg extracts and microinjection studies in human cells have suggested an additional function for Cdk2 in activation of Cdk1 and entry into mitosis. To further examine the role of Cdk2 in human cells, we generated stable clones with inducible expression of wild-type and dominant-negative forms of the enzyme (Cdk2-wt and Cdk2-dn, respectively). Both exogenous proteins associated efficiently with endogenous cyclins. Cdk2-wt had no apparent effect on the cell division cycle, whereas Cdk2-dn inhibited progression through several distinct stages. Cdk2-dn induction could arrest cells at the G1/S transition, as previously observed in transient expression studies. However, under normal culture conditions, Cdk2-dn induction primarily arrested cells with S and G2/M DNA contents. Several observations suggested that the latter cells were in G2 phase, prior to the onset of mitosis: these cells contained uncondensed chromosomes, low levels of cyclin B-associated kinase activity, and high levels of tyrosine-phosphorylated Cdk1. Furthermore, Cdk2-dn did not delay progression through mitosis upon release of cells from a nocodazole block. Although the G2 arrest imposed by Cdk2-dn was similar to that imposed by the DNA damage checkpoint, the former was distinguished by its resistance to caffeine. These findings provide evidence for essential functions of Cdk2 during S and G2 phases of the mammalian cell cycle.

[Cesar therapy is temporarily more effective in patients with chronic low back pain than the standard treatment by family practitioner: randomized, controlled and blinded clinical trial with 1 year follow-up]. / Cesar-therapie tijdelijk effectiever dan standaardbehandeling door de huisarts bij patiënten met chronische aspecifieke large rugklachten; gerandomiseerd, gecontroleerd en geblindeerd onderzoek met 1 jaar follow-up.

OBJECTIVE: To determine the effectiveness of a special form of exercise therapy ('Cesar therapy') on self reported recovery and improvement of posture amongst patients with chronic aspecific lower back pain. DESIGN: Prospective randomized controlled and blinded investigation. METHOD: After informed consent had been obtained, patients with chronic aspecific lower back pain were given, on a randomized basis, either an exercise therapy (experimental group, n = 112) or a standard treatment by their general practitioner (control group, n = 110). Outcome measures were self reported recovery of back pain and improvement of posture (thoracic and lumbar spine, pelvis). Self reported recovery was determined by means of a dichotomized 7-point scale (questionnaire). Posture was measured qualitatively by a panel of 11 Cesar therapists (blinded) and quantitatively by an optical-electronic posture recording system (Vicon). Measurements were taken at baseline (pre-randomization) and at 3, 6 and 12 months after randomization. RESULTS: Three months after randomization, patients who were treated according to Cesar therapy, reported an improvement in their back symptoms (80%) significantly more often than the control group (47%). In both groups, however, only small improvements in posture were found. The judgement of the Cesar panel exhibited a significant difference between the two groups, with respect to the spine, in favour of Cesar therapy. Differences between the groups were still present 6 months after randomization, but could no longer be detected at 12 months after randomization. CONCLUSION: Cesar therapy was significantly more effective than standard treatment among patients with chronic lower back pain for a period of 6 months after randomization.

LIN-5 is a novel component of the spindle apparatus required for chromosome segregation and cleavage plane specification in Caenorhabditis elegans.

Successful divisions of eukaryotic cells require accurate and coordinated cycles of DNA replication, spindle formation, chromosome segregation, and cytoplasmic cleavage. The Caenorhabditis elegans gene lin-5 is essential for multiple aspects of cell division. Cells in lin-5 null mutants enter mitosis at the normal time and form bipolar spindles, but fail chromosome alignment at the metaphase plate, sister chromatid separation, and cytokinesis. Despite these defects, cells exit from mitosis without delay and progress through subsequent rounds of DNA replication, centrosome duplication, and abortive mitoses. In addition, early embryos that lack lin-5 function show defects in spindle positioning and cleavage plane specification. The lin-5 gene encodes a novel protein with a central coiled-coil domain. This protein localizes to the spindle apparatus in a cell cycle- and microtubule-dependent manner. The LIN-5 protein is located at the centrosomes throughout mitosis, at the kinetochore microtubules in metaphase cells, and at the spindle during meiosis. Our results show that LIN-5 is a novel component of the spindle apparatus required for chromosome and spindle movements, cytoplasmic cleavage, and correct alternation of the S and M phases of the cell cycle.

The Caenorhabditis elegans gene ncc-1 encodes a cdc2-related kinase required for M phase in meiotic and mitotic cell divisions, but not for S phase.

We have identified six protein kinases that belong to the family of cdc2-related kinases in Caenorhabditis elegans. Results from RNA interference experiments indicate that at least one of these kinases is required for cell-cycle progression during meiosis and mitosis. This kinase, encoded by the ncc-1 gene, is closely related to human Cdk1/Cdc2, Cdk2 and Cdk3 and yeast CDC28/cdc2(+). We addressed whether ncc-1 acts to promote passage through a single transition or multiple transitions in the cell cycle, analogous to Cdks in vertebrates or yeasts, respectively. We isolated five recessive ncc-1 mutations in a genetic screen for mutants that resemble larval arrested ncc-1(RNAi) animals. Our results indicate that maternal ncc-1 product is sufficient for embryogenesis, and that zygotic expression is required for cell divisions during larval development. Cells that form the postembryonic lineages in wild-type animals do not enter mitosis in ncc-1 mutants, as indicated by lack of chromosome condensation and nuclear envelope breakdown. However, progression through G1 and S phase appears unaffected, as revealed by expression of ribonucleotide reductase, incorporation of BrdU and DNA quantitation. Our results indicate that C. elegans uses multiple Cdks to regulate cell-cycle transitions and that ncc-1 is the C. elegans ortholog of Cdk1/Cdc2 in other metazoans, required for M phase in meiotic as well as mitotic cell cycles.